Momordin Ic couples apoptosis with autophagy in human hepatoblastoma cancer cells by reactive oxygen species (ROS)-mediated PI3K/Akt and MAPK signaling pathways

Momordin Ic is a principal saponin constituent of Fructus Kochiae, which acts as an edible and pharmaceutical product more than 2000 years in China. Our previous research found momordin Ic induced Apoptosis by PI3K/Akt and MAPK signaling pathways in HepG2 cells. While the role of Autophagy in momordin Ic induced cell death has not been discussed, and the connection between the Apoptosis and Autophagy is not clear yet. In this work, we reported momordin Ic promoted the formation of autophagic vacuole and expression of Beclin 1 and LC-3 in a dose- and time-dependent manner. Compared with momordin Ic treatment alone, the Autophagy Inhibitor 3-methyladenine (3-MA) also can inhibit Apoptosis, while Autophagy activator rapamycin (RAP) has the opposite effect, and the Apoptosis inhibitor ZVAD-fmk also inhibited Autophagy induced by momordin Ic. Momordin Ic simultaneously induces Autophagy and Apoptosis by suppressing the ROS-mediated PI3K/Akt and activating the ROS-related JNK and P38 pathways. Additionally, momordin Ic induces Apoptosis by suppressing PI3K/Akt-dependent NF-κB pathways and promotes Autophagy by ROS-mediated ERK signaling pathway. Those results suggest that momordin Ic has great potential as a nutritional preventive strategy in Cancer therapy.